The aim of this study is to gather information about the absorption of known chemical carcinogens by epithelia of the mammalian colon. An extensive literature exists concerning the intracellular actions of chemical carcinogens in producing cancer of gastrointestinal epithelia and other tissues. Little is known, however, about the absorption of carcinogens from the intestinal lumen into the lining epithelia, or the absorption of carcinogens from the lumen into the blood. The primary carcinogens of interest will be 2-acetylaminofluorene; 2', 3-dimethyl-4-aminobiphenyl; N-methyl-N'-nitro-N-nitrosoguanidine; and 1,2-dimethylhydrazine. We propose to determine with reliable in vitro and in vivo techniques the following: 1) the mechanism of transport in the colon of four known carcinogens. Studies will be performed in vivo and in vitro to determine if net absorption or secretion takes place. Appropriate studies will indicate whether each carcinogen crosses the colonic mucosa by simple diffusion, facilitated transport, or some form of active transport. 2) the effects of bile acids and fatty acids on the transport of carcinogens across colon and into colon mucosal cells. This aim is specifically promoted in the Announcement of the Continuation of the National Large Bowel Cancer Project, FY 78 I.C. (10); page 5. Guinea pigs and rats will be the primary subjects of investigation. Some in vitro studies will be performed on human tissue removed at the time of surgery for purposes of comparison. Short of limiting carcinogens from the environment the most effective measure for reducing the incidence of cancer will be to limit entry of these substances into the body tissues. The information we propose to gather may serve as a base from which to design experiments on specifically limiting gastrointestinal absorption of chemical carcinogens. Thus, results of the proposed project might help us to understand, and begin a new approach to controlling environmental carcinogenesis associated with dietary factors.